Glucocorticoid Receptor α and β Variant Expression Is Associated with ASF/SF2 Splicing Factor Upregulation in HT-29 Colon Cancer and MCF-7 Breast Carcinoma Cells

Background and Aims. Transcriptional activity of NF-kappa B is inhibited by the liganded C glucocorticoid receptor (GR), which exists mainly in two splice variants as functional GR alpha and nonfunctional GR beta. We investigated the effect of 5-aza-2'-deoxycytidine (5-dAzaC), trichostatin A (TSA), and sodium butyrate (NaBu) on GR alpha,GR beta and ASF/SF2 splicing factor expression in HT-29 colon and MCF-7 breast carcinoma cells. Methods. HT-29 and MCF-7 cells were Cultured in the absence or in the presence of 5-dAzaC, TSA, and NaBu, followed by RNA and protein isolation. The transcript and protein levels of GR alpha, GR beta ASF/SF2 were determined by reverse transcription, real-time quantitative PCR and Western blot analysis. Results. We found that 5-dAzaC, TSA, and NaBu lead to an increase in GRa and ASF/SF2 transcript levels and a decrease in GRP transcript levels in HT-29 and MCF-7 cells. The 5-dAzaC, TSA, and NaBu resulted in increased GR alpha and ASF/SF2 protein levels and GRP protein downregulation in HT-29 cells. The most increased GR alpha protein expression in MCF-7 cells was observed with NaBu. However, all of these compounds inhibited GR beta protein expression in MCF-7 cells. The MCF-7 cells treated with NaBu demonstrated a remarkable increase in ASF/SF2 protein expression. Conclusions. Because NF-kappa B is considered to be a factor in the augmentation of malignant properties of cells, treatment of tumors with 5-dAzaC, TSA, and NaBu may provide a novel approach to the enhancement of therapeutic effects of glucocorticoids in epithelial carcinomas. (C) 2009 IMSS. Published by Elsevier Inc.